Expert Review of Gastroenterology & Hepatology最新文献

Introduction: A subset of gastrointestinal stromal tumors (GISTs) lacks the common mutations in KIT/PDGFRa genes. This is a rare and heterogeneous group of challenging GISTs due to their diversity and absence of sensitivity to the tyrosine kinase inhibitor (TKI) imatinib.

Areas covered: In this manscript, we review the pathogenesis, natural history, diagnostic features and management of KIT/PDGFRa wild-type (WT) GISTs, including SDH-deficient GISTs, GISTs with mutations in the RAS/RAF pathway, and quadruple WT GISTs which lack mutations in either KIT/PDGFRa and SDH genes or components of the RAS/RAF pathway, and syndromic GISTs as well as GISTs with rare KIT/PDGFRa mutations.

Expert opinion: Patients should be managed in reference centers. There has been progress in the understanding of the biology of these GISTs, and promising therapeutic targets have been identified. In SDH-deficient GISTs, the TKI olverembatinib has shown encouraging clinical activity but requires further clinical validation, while the HIF2a inhibitor bezultifan and temozolomide alone or in combination with the death receptor agonist 5 are under clinical investigation. Targeting the RAS/RAF pathway in RAS/RAF-mutated GISTs warrants evaluation in clinical trials. Rare molecular alterations in quadruple WT GISTs require investigation for their oncogenic potential. Collaborative research and patient advocacy is critical for these extremely rare tumors.

Introduction: Measurement of gastrointestinal (GI) transit is increasingly becoming a valuable tool in understanding the pathophysiology of symptoms of many digestive diseases, including irritable bowel syndrome (IBS). The objective of this article is to review the relevance of GI transit abnormalities for symptoms of IBS. These abnormalities relate to gastric emptying, small bowel transit, and colonic transit (whole gut transit).

Areas covered: The article briefly describes the current methods of assessment, factors that influence the result of these methods and the relationship of abnormalities of GI transit with symptoms that have been reported in IBS patients. Finally, a recommendation to guide the application of transit studies in IBS in both clinical practice and research is provided.

Expert opinion: Gastrointestinal transit is relevant to symptoms of bowel habits (stool frequency and form) and the relevance for other GI symptoms in IBS is not straightforward and needs further characterization. Intervention studies in IBS that incorporate objective measures of gut transit alongside symptom evaluation are warranted. Incorporating artificial intelligence into the methods of measuring transit could improve accuracy and simplify the measurements.

Introduction: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Photon radiotherapy shows efficacy in treating HCC but carries risks of high exit dose and radiation-induced liver disease. Additionally, HCCs with portal vein tumor thrombosis (PVTT) have a poor prognosis and are associated with higher risk of death. In recent years, proton beam therapy (PBT) has emerged as a novel treatment with the ability to downstage HCC for liver transplant (LT).

Areas covered: This review will provide an overview of dosimetric benefits of PBT, efficacy of PBT in treating HCC, downstaging HCC-PVTT for LT, and a comparison of PBT with other non-surgical techniques. A search of PubMed until 3 September 2024 was conducted using free search and the following keywords: hepatocellular carcinoma, proton beam therapy, portal vein tumor thrombosis, local ablative therapy, trans-arterial chemoembolization, stereotactic body radiotherapy, Y-90 radioembolization.

Expert opinion: Various clinical trials using PBT have shown promising tumor local control and overall survival rates. PBT is mostly safe and efficacious for downstaging HCC-PVTT for LT. PBT has also been shown to be non-inferior to various other treatment modalities. Future research should focus on combinations of PBT with other modalities.

Introduction: This systematic literature review (SLR) aims to compare the clinical, humanistic, and economic outcomes associated with specialized and standard nutritional formulas for the treatment of mild-to-moderate pediatric Crohn's disease.

Methods: Search strategies were applied across MEDLINE, Cochrane and Web of Science (January 2000-October 2023) and recent congress proceedings (January 2021-October 2023). PRISMA-P guidelines were followed. Quality assessment evaluated risk of bias.

Results: Twenty-three unique studies met the inclusion criteria. Nineteen studies (754 patients) evaluated specialized formula, 10 assessed standard formula (246 patients). Mucosal healing (7 studies), induction (20 studies) and maintenance of remission (9 studies) were reported over various timeframes. High proportions of patients who received specialized formula achieved mucosal healing (63-89% 8 weeks; 25-74% 10 weeks), and remission (50-100% 8 weeks). Specialized formula sustained remission (34-62.5% 6 months and 24-87.5% 1 year). Results were not directly comparable with standard formula due to significant heterogeneity in study methodology, patient populations, and remission definition.

Conclusions: The evidence predominantly supports the benefits of specialized formula in inducing mucosal healing, remission, and sustaining positive outcomes across multiple timepoints. Direct comparison of nutritional interventions is required to further support the findings of this SLR.Protocol registration: PROSPERO CRD42023472370.

Introduction: The management of inflammatory bowel disease (IBD) has evolved substantially over the past decade, with the emergence of new advanced therapies presenting unprecedented challenges in clinical decision-making. While these therapies provide patients with more opportunities to get better, biomarkers to guide their use remain elusive.

Areas covered: This article highlights the challenges associated with biomarker discovery, interpretation, and application in IBD - based on literature review, first-hand experience of biomarker discovery, and personal opinion. We highlight problems including the misinterpretation of predictive capabilities, lack of independent validation, and reverse causation in retrospective studies, and explain why associations with clinical parameters or seropositivity to microbial antigens often fail to meet the rigorous performance metrics required for clinical utility. The relative need for different biomarkers is also discussed - particularly in light of recent evidence from the PROFILE trial, which emphasizes the considerably greater risk posed by uncontrolled disease than by the potential side-effects of medications.

Expert opinion: Despite multiple challenges, the potential of biomarkers for precision medicine in IBD remains promising, particularly in combination with other clinical and biochemical parameters. Further research into combinatorial biomarker approaches is needed, but must be combined with learning how to communicate results that are inherently uncertain.

Background: We assessed the use of large language models (LLMs) like ChatGPT-3.5 and Gemini against human experts as sources of patient information.

Research design and methods: We compared the accuracy, completeness and quality of freely accessible, baseline, general-purpose LLM-generated responses to 20 frequently asked questions (FAQs) on liver disease, with those from two gastroenterologists, using the Kruskal-Wallis test. Three independent gastroenterologists blindly rated each response.

Results: The expert and AI-generated responses displayed high mean scores across all domains, with no statistical difference between the groups for accuracy [H(2) = 0.421, p = 0.811], completeness [H(2) = 3.146, p = 0.207], or quality [H(2) = 3.350, p = 0.187]. We found no statistical difference between rank totals in accuracy [H(2) = 5.559, p = 0.062], completeness [H(2) = 0.104, p = 0.949], or quality [H(2) = 0.420, p = 0.810] between the three raters (R1, R2, R3).

Conclusion: Our findings outline the potential of freely accessible, baseline, general-purpose LLMs in providing reliable answers to FAQs on liver disease.

Introduction: Hepatocellular carcinoma (HCC) remains a major global health concern, as it is the most common primary liver cancer and the fourth leading cause of cancer-related mortality.

Areas covered: Immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm, offering promising survival outcomes. However, the controlled conditions of randomized clinical trials (RCTs) often fail to reflect real-world complexities, emphasizing the necessity for strong real-world evidence (RWE). RWE, in most cases derived from observational studies, provides critical insights into the effectiveness, safety, and tolerability of systemic therapies across diverse populations and settings. The authors searched MEDLINE, Ovid Embase, and Scopus for full-text published articles in any language from the inception to 30 June 2024.This review evaluates RWE on systemic therapies for advanced HCC, including tyrosine kinase inhibitors (TKIs) like sorafenib and lenvatinib, ICIs such as nivolumab and pembrolizumab, and combination therapies like atezolizumab/bevacizumab and durvalumab/tremelimumab.

Expert opinion: Studies reveal discrepancies in treatment efficacy and adverse event profiles between RCTs and routine clinical practice, underscoring the need for individualized treatment strategies. RWE highlights the influence of liver disease etiology, liver function, and tumor burden on treatment outcomes, guiding therapy selection.

Introduction: Transition of care (TOC) is a process that must be planned and executed in a coordinated manner factoring patient, family, disease, and healthcare system. Among youth with gastrointestinal hereditary polyposis syndromes (HPS), poorly planned TOC can have devastating consequences from poor engagement in necessary medical care. This results in increased risk of cancer and related mortality. This review aims to emphasize unique aspects of HPS relevant to TOC, related barriers/challenges, and outline current best practice recommendations.

Areas covered: A review was undertaken of transition-focused practice guidelines among youth with chronic conditions, as well as literature from major pediatric gastroenterology societies on the ideal approach for managing polyposis syndromes. Literature from PubMed and Medline, including conference abstracts and proceedings, was reviewed and in the absence of empirically supported evidence, recommendations reflect the opinion of the author experts involved in the care of adolescents and young adults (AYA) with HPS.

Expert opinion: Effective TOC requires a structured, patient-centered, individualized process that includes early engagement, incremental education, and multidisciplinary collaboration. Given the unique aspects of HPS, including complex psychosocial and medical needs, there is urgent need for research toward evidence-based strategies enhancing continuity, and mitigating socio-cultural and financial barriers to care.

Introduction: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic condition characterized by abnormal immune responses and intestinal inflammation. Emerging evidence highlights the vital role of gut microbiota in IBD's onset and progression. Recent advances have shaped diagnostic and therapeutic strategies, increasingly focusing on microbiome-based personalized care. Methodology: this review covers studies from 2004 to 2024, reflecting the surge in research on luminal microbial ecology in IBD. Human studies were prioritized, with select animal studies included for mechanistic insights. Only English-language, peer-reviewed articles - clinical trials, systematic reviews, and meta-analyses - were considered. Studies without clinical validation were excluded unless offering essential insights. Searches were conducted using PubMed, Scopus, and Web of Science.

Areas covered: we explore mechanisms for managing IBD-related microbiota, including microbial markers for diagnosis and novel therapies such as fecal microbiota transplantation, metabolite-based treatments, and precision microbiome modulation. Additionally, we review technologies and diagnostic tools used to analyze gut microbiota composition and function in clinical settings. Emerging data supporting personalized therapeutic strategies based on individual microbial profiles are discussed.

Expert opinion: Standardized microbiome research integration into clinical practice will enhance precision in IBD care, signaling a shift toward microbiota-based personalized medicine.